13alpha-androst-5-ene-3beta, 17alpha-diol and esters thereof



, ducing BB-hydroxy-l3oz-androst-5-en-17-one [Rec Trav. Chim. desPays-Bas, 77, 1010 (1958)] with lithium aluminum hydride or theequivalent (for example, sodium United States Patent 3,153,062130t-AROST-=5-ENE-3fl,l70t-DIOL AND ESTERS THEREUF Leland J. Chinn,Morton Grove, Ill, assignor to G. D. earle & C0,, Chicago, ill., acorporation of Delaware No Drawing. Filed July 20, 1962, Ser. No.211,404

4 Claims. (Cl. 260-3975) This invention relates tol3a-androst-5-ene-3fl,17-diols, esters thereof, and processes wherebythese diols and their esters can be prepared. More particularly, thisinvention provides new and useful chemical compounds of the formulawherein R represents hydrogen or an alkanoyl radical and the ORsubstituent on carbon atom number 17 can be in either a or ,8configuration.

Among the alkanoyl radicals represented by R especial- 1y lower alkanoylradicals are preferred, which is to say, radicals of the formula-CO-lower alkyl in which lower alkyl designates a methyl, ethyl, propyl,isopropyl, butyl, sec-butyl, tert-butyl, pcntyl, neopentyl, hexyl,isohexyl, heptyl, or like saturated, acyclic, straightor branched-chain,monovalent, hydrocarbon grouping of the formula wherein n represents apositive integer less than 8.

The compounds to which this invention relates are useful by reason oftheir valuable and unexpected pharmacological properties. Thus, forexample, 3,8,17oc-diace- -toxy-lh-androsbS-ene, a representative esterderiving from the corresponding 3/3,17-diol, is an antiprogesterone.Distinct from the 13,8,17fl-epimer of the prior art, it inhibitsprogesterone-induced uterine arborization.

Preparation of the subject compounds proceeds by redes . skilled in theart of organic synthesis that many modifications, both of materials andof methods, may be practiced without departing from the purpose andintent of this disclosure. Throughout the examples hereinafter setvforth, temperatures are given'in degrees centigrade and relativeamounts of materials in parts by weight, except as otherwise noted.Specific rotations are at 25 and re- 'ferred to the D line of sodium.

Example 1 13a-androst-5 ene-3fl,17ot-di0l.To a mixture of 1 part oflithium aluminum hydride and 70 parts of anhydrous ether at the boilingpoint under reflux is added, with agitation during A hour, a solution of1 part of 3,8-hydroxy- 13a-androst-5-en-17-one in a mixture ofapproximately 6 parts of tetrahydrofurfan and 98 parts of anhydrousether. The resultant mixture is maintained at the boiling point underreflux with agitation for 18 hours, then chilled to 0-5, decomposed withwater, and acidified with 5% hydrochloric acid. The ethereal phase isseparated and successively washed with 5% hydrochloric acid, water, anda saturated aqueous solution of sodium chloride, then dried overanhydrous sodium sulfate and stripped of solvent by vacuum distillation.The solid residue, upon repeated crystallization from ether, affords13a-androst-5- ene-3fi,17o-diol as colorless plates melting atapproximately 192193 and further characterized by a specific rotation of122 in 1% chloroform solution. The product has the formula Example 213a-andr0st-5-ene-35J7-diol.The mother liquors deriving from thecrystallization of 13u-androst-5-ene3{3, l7a-diol in Example 1 arecombined and stripped of solvent by vacuum distillation. The residue,recrystallized from a mixture of ether and pentane, affords colorlesslaths melting at approximately 1625-1635 and having a specific rotationin 0.5% chloroform solution of 99.-

The product thus obtained is IBfi-androst-S-ene-SB,175

' .diol, of the formula Example 3 3/3,]7ot-diacet0xy-13a-androst-5-ene-Asolution of 10 I parts of 13a-androst-5-ene-3,8, 17a-diol in a mixtureof 42 parts of pyridine and 42 parts of acetic anhydride is al lowed tostand at room temperature for 20 hours, then diluted with ice water. Theoil which precipitates solidifies on standing. Filtered off, washed withwater, dried in air, and crystallized from aqueous methanol, it affords3 5,17 u-diacetoxy-13oc-androst-5-ene as colorless massive rhombsmelting at approximately 93-935 and having a specific rotation of -109.5in 1% chloroform solution. The product has the formula ll o-c-onaExample 4 of 20 parts of 13ot-androst-5-ene 3fi,17a-diolin a mixture of177 parts of pyridine and 179 parts of propionic anhydride is allowed tostand at room temperatures for 18 hours, then poured into 5 volumes ofice water. The mixture thus obtained is acidified With 5% hydrochloricacid. The oil thrown down solidifies on standing. Filtered off, Washedwith water, dried in air, and recrystallized from aqueous methanol, italfords 3,8,17a-dipropionyloxy-13a-androst-5-ene as colorless rodsmelting at approximately 74-75". The product has the formula 4 What isclaimed is: 1. A compound of the formula Hm I I 0 R0- wherein Rrepresents a member of the class consisting of hydrogen and loweralkanoyl radicals.

2. 13a-androst-S-ene-ElfiJ7cc diol. 15 3.3B,17a-diacetoxy-13a-androst-5-ene.

4. 3,8,17oc-dipropionyloxy-l3a-androst-5-ene.

References Cited in the file of this patent Jones et al.: J.A.C.S., vol.70, 1948, pp. 2024-2034 (Q1) 1 A 5).

1. A COMPOUND OF THE FORMULA